PLACI is a recently described X-linked gene that is expressed exclusively by cells of trophoblastic origin in placental tissue. A significant role for PLACI in placental development is strongly suggested by its tissue-specific and temporal pattern of expression. This suggestion is strengthened by a fetal growth retardation phenotype associated with X chromosome deletions in the region to which PLAC1 maps. Additional, independent studies have also suggested that this region of the X chromosome contains gene(s) important in placental growth. Computer assisted analysis of this region of the X chromosome suggests PLACI is the leading candidate gene responsible for placental abnormalities associated with these gene deletions. PLAC1 shares sequence homology with the zona pellucida protein 3 (ZP3) suggesting that it may be involved in specific cellular interactions at the maternal-fetal interface, possibly acting as a cell surface receptor. Viewed collectively, these observations strongly suggest that PLAC1 encodes a placenta-specific extracellular protein of major importance to mammalian reproduction. It is likely, therefore, to serve as an important marker for placental and fetal well-being. The proposed studies will develop a mouse Placl knockout model to define its role in placental development. Additionally, PLAC1 expression will be studied as a function of trophoblast differentiation will be studied in normal human trophoblasts. Finally, human PLAC1 protein will be expressed, characterized, and its potential receptor function studied. These studies will provide new insights into mechanism important to placental growth and function, and will form the basis for future studies aimed at defining the role of PLAC1 at the cellular level.